Compounds and methods for regulating cell differentiation

• US 6,908,732 B2
• Filed: 10/15/2001
• Issued: 06/21/2005
• Est. Priority Date: 10/13/2000
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Falchuk, Kenneth H.
• Primary Examiner(s): Witz, Jean C.
• Assistant Examiner(s): HANLEY, SUSAN MARIE
• Application Number:
  US09/977,866
• Publication Number:
  US 20020099085A1
• Time in Patent Office: 1,345 Days
• Field of Search: 435/1.1, 435/325, 514/359, 514/422
• US Class Current: 435/1.1
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555

Abstract

The present invention makes available methods and reagents for inhibiting cell growth or promoting cell differentiation comprising contacting the cell with a differeguline in a sufficient amount to inhibit cell proliferation or promote cell differentiation.

Claims

1. A method for promoting colon adenocarcinoma cell differentiation, comprising treating a colon adenocarcinoma cell with a bilin.

7. The method of claim 1, wherein the bilin is bilirubin or biliverdine.

2. A method for promoting differentiation of a colon adenocarcinoma cell, comprising treating a colon adenocarcinoma cell with a bilin represented by the general formula (I):

wherein

W represents —

CL₂—

, —

C(═

O)—

, —

C(═

S)—

, —

C(═

NH)—

, or ═

CL—

;

X represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

Y represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

Z represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

A represents —

NH—

or —

N═

;

B represents a trisubstituted, sp²-hybridized carbon atom;

K represents =CL—

or —

CL₂—

; and

L represents H or lower alkyl.

3. The method of claim 2, wherein the cell is contacted with the bilin in vitro.

4. The method of claim 2, wherein the cell is contacted with the bilin in vivo.

5. The method of claim 4, wherein the bilin is administered as part of a therapeutic application.

8. The method of claim 2, wherein the bilin is bilirubin or biliverdine.

6. A method for promoting colon adenocarcinoma cell differentiation, comprising administering to a patient a pharmaceutical preparation comprising a sterile pharmaceutical excipient and a bilin.

9. A method for promoting colon adenocarcinoma cell differentiation, comprising administering to a patient a pharmaceutical preparation comprising a sterile pharmaceutical excipient and a bilin represented by the general formula (I):

wherein

W represents —

CL₂—

, —

C(═

O)—

, —

C(═

S)—

, —

C(═

NH)—

, or ═

CL—

;

X represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

Y represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

Z represents a substituted or unsubstituted alkyl, alkenyl, or alkynyl group;

A represents —

NH—

or —

N═

;

B represents a trisubstituted, sp²-hybridized carbon atom;

K represents =CL—

or —

CL₂—

; and

L represents H or lower alkyl.